266 INFLUENCE OF DEXAMETHASONE AND ACTH ON DRUG CLEARANCE IN CHILDREN

Abstract

The rate of disappearance of antipyrine from the plasma is a useful indicator for the in vivo capacity for hepatic mixed function oxidation. The short term effects of systemic administration of dexamethasone, a potent glucocorticoid, and ACTH on antipyrine metabolism were studied in 10 children. Dexamethasone (2 mg/d × 4 days) was given to 6 subjects. The effects of ACTH (40 U/24 h i.v. × 5 days) were evaluated in 4 patients. The half-life of antipyrine (t½) was measured before and after drug therapy in each patient. The mean t½ was not affected by administration of dexamethasone (t½ 7.6 ± 1.14 h versus 7.8 ± 0.84 h). The apparent volume of distribution (aVd) remained unchanged as well (aVd 0.52 ± 0.076 L/kg versus 0.56 ± 0.063 L/kg). Administration of ACTH, causing a 5-25 fold increase in urinary 17-hydroxy-corticosteroid excretion, also did not affect the half-life of antipyrine (t½ 11.5 ± 2.8 h versus 11.2 ± 2 h). The aVd also remained unchanged (0.60 ± 0.05 L/kg versus 0.59 ± 0.03 L/kg). We conclude that the short term administration of dexamethasone and ACTH with ensuing stimulation of endogenous glucocorticoid production is unlikely to produce clinically significant changes in the rate of drug metabolism.